Chemotherapeutic agents are frequently used in the clinical treatment of many forms of tumors. Information regarding whether a given tumor cell is susceptible (i.e., sensitive) or resistant to a particular chemotherapeutic agent is critical. Provided in advance, this information greatly enhances a physician's ability to implement proper dosages to kill the tumor cells. In addition, such information permits swift changes in treatment regimes and therefore avoids toxic side effects of the chemotherapeutic agent if the tumor cell proves to be chemotherapy resistant. Where a given tumor is initially sensitive to chemotherapy agents but develops resistance over the course of treatment, it becomes necessary to gain information about the susceptibility change.
There have been several disclosed tests whose goals are to predict tumor sensitivity to chemotherapy agents. One early test is based on the observation in 1954 that the ability of chemotherapy agents to reduce cellular metabolism could be monitored by measuring tetrazolium blue reduction by fresh tumor biopsy materials. (Black et al., J. Nat'l Cancer Inst. 14, 1147-1158 (1954)). Most other tests correlate chemo-sensitivity to a particular intracellular chemical. For example, U.S. Pat. No. 5,366,885 discloses the use of elevated glutathione to predict tumor drug sensitivity. To overcome false-negative or false-positive results, however, a four-tiered confirmatory testing is required. This cumbersome biochemical tests render the approach undesirable.
U.S. Pat. No. 5,270,172 discloses an in vitro method that utilizes estrogen and anti-estrogen and requires quantifying cell growth inhibition under these culture conditions. U.S. Patent Appl. No. 2006/0172305 discloses a method of measuring susceptibility via a glucose transporter. U.S. Pat. No. 6,949,359 discloses chemosensitivity determination using one marker whose specific binding capability to phosphatidylserine can be detected. U.S. Pat. No. 7,344,829 discloses a method for detecting the efficacy of anti-cancer treatment by comparing growth factor receptor phosphorylation. While all these assays may provide a measure of predictability to the question of tumor drug resistance, they often require long assay duration and lack reliability. Thus, there exists an unfulfilled need for a predictive assay for drug resistance, which provides rapid, reliable results for a spectrum of possible chemotherapy agents.
A method of determining drug susceptibility profile for a particular tumor (prior to the administration of chemotherapy agents) is highly desirable. However, there has been no suggestion in the art relating to a method of using virus as a means to determine tumor cell susceptibility to chemotherapy agents. There has also been no information relating the application of herpes simplex virus as a vehicle to assess drug susceptibility. The present inventors have surprisingly discovered that herpes simplex virus lacking an immediate early gene is a novel and reliable indicator for use in determining tumor cell susceptibility to chemotherapeutic agents.